rs1566347

Variant names:

• chr4-185811412-T-C
• rs1566347
• NM_001395207.1:c.-237+252A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395207.1(SORBS2):​c.-237+252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 152,042 control chromosomes in the GnomAD database, including 36,289 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36289 hom., cov: 32)
• Consequence: SORBS2 NM_001395207.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 6 publications found

Genes affected

SORBS2 (HGNC:24098): (sorbin and SH3 domain containing 2) Arg and c-Abl represent the mammalian members of the Abelson family of non-receptor protein-tyrosine kinases. They interact with the Arg/Abl binding proteins via the SH3 domains present in the carboxy end of the latter group of proteins. This gene encodes the sorbin and SH3 domain containing 2 protein. It has three C-terminal SH3 domains and an N-terminal sorbin homology (SoHo) domain that interacts with lipid raft proteins. The subcellular localization of this protein in epithelial and cardiac muscle cells suggests that it functions as an adapter protein to assemble signaling complexes in stress fibers, and that it is a potential link between Abl family kinases and the actin cytoskeleton. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

SORBS2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SORBS2	NM_001395207.1	c.-237+252A>G		intron_variant	Intron 1 of 26	ENST00000695409.1	NP_001382136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SORBS2	ENST00000695409.1	c.-237+252A>G		intron_variant	Intron 1 of 26		NM_001395207.1	ENSP00000511888.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104898 AN: 151924 Hom.: 36269 Cov.: 32

Gnomad AFR AF: 0.694

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.723

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.690 AC: 104975 AN: 152042 Hom.: 36289 Cov.: 32 AF XY: 0.692 AC XY: 51451 AN XY: 74308

African (AFR) AF: 0.694 AC: 28761 AN: 41450

American (AMR) AF: 0.718 AC: 10973 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2580 AN: 3468

East Asian (EAS) AF: 0.733 AC: 3784 AN: 5160

South Asian (SAS) AF: 0.683 AC: 3288 AN: 4814

European-Finnish (FIN) AF: 0.691 AC: 7290 AN: 10556

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45904 AN: 67994

Other (OTH) AF: 0.725 AC: 1526 AN: 2106

Alfa AF: 0.687 Hom.: 70815

Bravo AF: 0.692

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.1
DANN	Benign	0.36
PhyloP100		-0.41
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1566347; hg19: chr4-186732566;